ICH-E2E guideline was published on November 18, 2004. In Japan, it has been notified on September 16, 2005 as “Pharmacovigilance Planning”. Then, in parallel with the system development of PMDA is advanced, Ministry of Health, Labour and Welfare revised the notification, it was announced the “Risk Management Plan Guideline” on April 2012. Based on this Guideline, Marketing Authorization Holder creates a whole plan of post-marketing safety measures. This plan is the Japanese RMP (J-RMP). “Risk Management Plan Guideline” are created by the reference to REMS in US and EU-RMP, and modified in consideration of the real situation in Japan. Then, GVP Ordinance and GPSP Ordinance were revised on March 11, 2013. As the result, since October 2014, implementation and creation of the RMP was mandated. At the end of November 2014, 65 RMPs has already been published on Website of PMDA. J-RMP has been positioned as an important system for strengthening of post-marketing safety measures. Published versions of J-RMPs are summarized in compact an overall picture of the post-marketing safety measuresfor respective new drugs. It is also including planned time-line of post-marketing surveillance or post-marketing clinical study. By all stakeholders get a better understanding, it is expected thatthe J-RMP is steadily perform.

Thrombomodulin is an endothelial cell membrane protein that is released into the blood in soluble forms in response to endothelial damage. We evaluated thrombomodulin in blood samples taken from the femoral vein before, during and after elective surgery for abdominal aortic aneurysm in 9 patients. Thrombomodulin was measured using an ETA assay. Thrombomodulin decreased significantly just before aortic declamp from before surgery (p<0.001), and remained unchanged just after and 1 hour after aortic declamp. Three hours after aortic declamp, thrombomodulin increased significantly from 1 hour after aortic declamp (p<0.01), peaked at 6 hours after aortic declamp and then decreased. These data suggest that thrombomodulin did not increase significantly during surgery for abdominal aortic aneurysm.

Anastomotic false aneurysm (AFA) of the aorta or iliac artery is a rare but life-threatening complication of prosthetic grafts. We report a surgical case involving AFA of the right external iliac artery which developed at the site of peripheral anastomosis of the temporary bypass procedure used during prosthetic reconstruction of the descending aorta for dissecting aneurysm (DeBakey IIIb) 15 years previously. A 60-year-old woman was hospitalized with rapidly growing right lower abdominal mass. Computed tomography and angiography revealed that the mass was an anastomotic external iliac artery false aneurysm and surgery was performed. The AFA was exposed transperitoneally and resected with a part of the intact external iliac artery without complication. Anatomical reconstruction was completed with a prosthesis. The postoperative course was uneventful. We conclude that patients with retroperitoneal grafts require lifelong routine periodic follow-up and if an AFA is discovered, it should be resected.

We experienced unusual dilatation of gelatin-impregnated knitted Dacron prostheses after abdominal aortic aneurysm surgery. Therefore, we investigated dilatation of gelatin impregnated knitted Dacron grafts compared with other types of Dacron grafts after abdominal aortic aneurysm surgery. Eighteen grafts inserted after abdominal aortic aneurysm surgery were studied for to evaluate dilatation. Enhance CT was used to determine the external diameter of the most dilated portion of the abdominal aortic grafts and high speed plain CT was used to determine the most dilated internal diameter. The gelatin-impregnated knitted Dacron grafts dilated from 25% to 43.8% (mean 31.8±7.2%), significantly more than collagen impregnated woven Dacron grafts (p=0.0003). Moreover, high fever was frequently noticed after these grafts implantation (66.7%). Therefore, caution must be used concerning these implantation in aortic lesions and careful follow-up study should be performed after implantation.

We encountered an unusual disruption of an expanded polytetrafluoroethylene (EPTFE) axillofemoral bypass graft apart from that anastomoses. We suspected the possible robe of the physical effects of body movement provoking the disruption of the axillofemoral bypass graft and therefore examined the physical effect of body movement on the axillary-to-femoral artery graft in 15 healthy men. At the lower part of the graft, the physical effect was significantly stronger. The disruption of this axillary-to-femoral artery graft was associated with the physical effect of body movement.

The purpose of this study was to determine the effect of intraoperative autologous blood salvage during elective abdominal aortic aneurysm repair with Cell Saver 4 (Heamonetics Inc.). Fifty patients prospectively received intraoperative autologous transfusion (Group CS; n=50, 1991-94) and 25 received no intraoperative autologous transfusion (Group NCS; n=25, 1983-91). Only 7 patients in Group NCS received no homologous blood (28%), while 43 in Group CS received autologous blood transfusion (86%). There was no difference between the groups with respect to postoperative platelets counts or serum concentrations of total protein, albumin, BUN and LDH. We conclude that the use of the Cell Saver 4 reduces perioperative homologous blood during elective aortic aneurysm repair.

Objective: We conducted a questionnaire survey to comprehend the situation regarding the collection, provision, and utilization of drug safety information at hospitals.  In addition, we asked pharmaceutical companies how they select medical institutions to provide drug safety information.  We also investigated the current situation of information provision to Tokyo Medial Center by pharmaceutical companies.
Method: A questionnaire was mailed to all hospitals in Japan.  The survey was conducted between January 13 and February 10, 2011.  Moreover, we asked thirteen pharmaceutical companies by telephone and e-mail about the implementation status of the provision of information and performed a survey at Tokyo Medical Center on the current situation of information provision by pharmaceutical companies regarding revisions to precaution sections in package inserts.
Results: The results of the questionnaire survey (response rate: 41.2%) showed that the major information sources for hospitals were medical representatives (77.8%), Drug Safety Update (50.3%) and direct mails (49.3%).  Furthermore, in the case of drugs prescribed exclusively for extramural dispensing, fewer hospitals responded that medical representatives of the pharmaceutical companies provided drug safety information and more hospitals responded that they did not obtain any drug safety information at all, compared with drugs listed in the hospital formularies.
Conclusion: To minimize the risks of drugs, healthcare professionals must collect a wide range of drug safety information and must utilize this information in their medical practice.  Therefore, it is important that pharmaceutical companies and regulatory authorities make an effort to provide suitable information dissemination to medical institutions.  Furthermore, medical institutions must also strengthen their systems for collecting drug safety information and providing such information to healthcare professionals.

Background: In one series of studies, we observed the effects of acupuncture treatment (AT) on the autonomic nerve system (ANS). We experimented from various view-points. At last, we discovered a specific pattern for modifying ANS status, which showed that functions of the parasympathetic nerve increased while those of the sympathetic nerve decreased. To further study systematic modification of ANS balance, we focused on the lower body (feet). Moreover, two kinds of stimuli, tapping and vibration, were applied while measuring the value of finger floor distance (FFD) and heart rate (HR). Finally, the effects on ANS were discussed. Methods: Twenty healthy subjects participated in this study, and they were divided into two groups; the tapping group and the vibration group. The former received 50 taps on the feet, and the latter received vibrations for two minutes. In order to indicate ANS status the effects of these stimuli were evaluated by FFD values and a kinetic record of changes in HR. Results: Both groups showed improvement in FFD values, which was the same as the results for AT via modification of ANS. However, changes in HR showed a different pattern from AT; in this study sympathetic nerve) dominantly showed an increase without a decrease in parasympathetic nerve. Discussion and Conclusions: The reasons for differences in ANS modification may be found in the role, especially in an emergency, of the lower body. The lower body is heavy in skeletal muscles, which needs energy and blood to react during acute stress. The ANS, which controls blood distribution, may shift and concentrate system blood from the smooth muscles of the stomach (controlled by parasympathetic nerve) to the skeletal muscles of the legs and feet (controlled by sympathetic nerve). Thus, this study indicated that local stimuli of the foot induced systematic ANS modification.

Objective: We investigated the effects and the mechanism of the acupuncture. Methods: Nishijo/Mori and colleagues studied the function of the autonomic nervous system (ANS) with the instantaneous heart rate (IHR) as indicator. With the ANS blockers we also revealed the response of ANS when we insert needles to human body. For example, in our study of 1991, we conducted an experimental study on humans and elucidated that the physical stimulation promoted the resilience and the homeostasis of our body. Our recent study (2013) showed the physical stimulation (not acupuncture) on the lower thighs (mainly the bottom of the feet) also enhanced the above mentioned effects. Results and Discussion: 1.　The subjects sat on the chairs and they were given the acupuncture stimulation on their wrists (the skin and subcutaneous tissues) at the expiration. The stimulation for the duration of 15 consecutive breaths increased the function of the parasympathetic nerve (PN). At the same time that of the sympathetic nerve (SN) also enhanced. In short, firstly that of PN enhanced and secondly that of SN followed. Thus, it was observed that the physical stimulations promoted the resilience and the homeostasis of our body and we may regard that this is the first mechanisms. 2.　In our recent study (2013) the subjects sat on the chairs and there were given the stimulation (50 times of fist-strikes) on the sole of the feet. Immediately after the stimulation the result of Floor Finger Distance test （FFD) was improved. At the same time IHR, the indicator of the function of ANS, showed that those of SN (adrenaline β stimulus) and PN were simultaneously increased as soon as the stimulation started. The same result was obtained from the study of the body vibration (the SOUND healing). This process of 2013 was different from that of 1991, however, both of them provided the effect; the promotion of the resilience and the homeostasis of our body. Therefore, we could regard it as the second mechanism of the physical stimulations which promotes the resilience and the homeostasis of our body. Conclusion: In this way, there are two mechanisms of the physical stimulation in promoting the resilience and the homeostasis of our body.

Drug dispensing is a statutory and designated duty of a pharmacist. We aimed to examine the changes in the nature of drug dispensing using a text mining method. Our corpus consisted of text documents from “Chozai Shishin”, the most standard manual for dispensing drugs in Japan, Editions 1 to 13 (Japan Pharmaceutical Association), and we used the KH Coder software for text mining. We constructed networks showing the association between frequent word co-occurrence and edition number, and co-occurrence relations for frequent words in each edition. We found that “patient” superseded “dispensing” as a frequent term over time. “Dispensing” was another frequent term with a highly centralized node in each edition. Accordingly, we targeted the term “dispensing” for network analysis to depict its co-occurrence relations. We found that the range of related words for “dispensing” broadened from “preparation” and “compounding” to include “patient adherence instructions”, “assessment”, “medical treatment”, and “information provision”. Accordingly, we concluded that the content of “dispensing”, which is a pharmacist’s duty, has expanded from the duties of “dispensing drugs” to include “responding to patients” within the definition of “dispensing”, and we were able to present this finding as objective data by using the mechanical method known as text mining.